Boretti F S, Leutenegger C M, Mislin C, Hofmann-Lehmann R, König S, Schroff M, Junghans C, Fehr D, Huettner S W, Habel A, Flynn J N, Aubert A, Pedersen N C, Wittig B, Lutz H
Department of Veterinary Internal Medicine, University of Zurich, Switzerland.
AIDS. 2000 Aug 18;14(12):1749-57. doi: 10.1097/00002030-200008180-00009.
To evaluate the efficacy of a genetic vaccination protocol based on minimalistic, immunogenic defined gene expression (MIDGE) vectors coding for domains of the feline immunodeficiency virus (FIV) env gene and feline IL-12.
Three groups of four cats each were immunized three times within 6 weeks by the ballistic transfer of gold particles coated with MIDGE vectors. Group 1 received non-coated gold beads, groups 2 and 3 MIDGE vectors expressing FIV surface plus part of the transmembrane protein. In addition, group 3 received feline IL-12 DNA. All cats were challenged by intraperitoneal injection of 25 TCID50 of infectious FIV Z2. The following criteria were monitored: clinical signs, antibodies to transmembrane protein, antibodies to whole FIV, haematological parameters and kinetics of CD4 and CD8 cells, FIV proviral load (determined by quantitative polymerase chain reaction; PCR) and cytotoxic T lymphocyte (CTL) activity (in selected cats).
None of the cats developed a detectable antibody response during immunizations. Four weeks after challenge exposure, all cats in group 1 (control) and group 2 (FIV surface-transmembrane protein) had seroconverted and showed a high proviral load until week 19 (end of experiment). In contrast, only one of four cats in group 3 (surface-transmembrane protein and IL-12) showed antibodies; it was provirus positive at reduced virus load. Short-lived CTL activity was found in two cats in group 3.
Genetic vaccination using a MIDGE-based construct for the expression of the surface-transmembrane protein domain of FIV env and feline IL-12 DNA led to protection against homologous virus challenge in three out of four vaccinated cats.
评估基于编码猫免疫缺陷病毒(FIV)env基因结构域和猫白细胞介素-12(IL-12)的简约、免疫原性明确基因表达(MIDGE)载体的基因疫苗接种方案的疗效。
三组猫,每组四只,在6周内通过包被有MIDGE载体的金颗粒的基因枪转移法进行三次免疫接种。第1组接受未包被的金珠,第2组和第3组接受表达FIV表面蛋白加部分跨膜蛋白的MIDGE载体。此外,第3组接受猫IL-12 DNA。所有猫通过腹腔注射25个感染性FIV Z2的半数组织培养感染剂量(TCID50)进行攻毒。监测以下标准:临床症状、针对跨膜蛋白的抗体、针对全FIV的抗体、血液学参数以及CD4和CD8细胞的动力学、FIV前病毒载量(通过定量聚合酶链反应;PCR测定)和细胞毒性T淋巴细胞(CTL)活性(在选定的猫中)。
在免疫接种期间,没有一只猫产生可检测到的抗体反应。攻毒暴露后四周,第1组(对照组)和第2组(FIV表面 - 跨膜蛋白组)的所有猫都发生了血清转化,并在第19周(实验结束)前显示出高前病毒载量。相比之下,第3组(表面 - 跨膜蛋白和IL-12组)的四只猫中只有一只显示出抗体;其前病毒呈阳性,但病毒载量降低。在第3组的两只猫中发现了短暂的CTL活性。
使用基于MIDGE的构建体表达FIV env的表面 - 跨膜蛋白结构域和猫IL-12 DNA进行基因疫苗接种,在四分之三的接种猫中产生了针对同源病毒攻毒的保护作用。